The goal of this laboratory is to develop, evaluate, and implement new probes to examine the chemistry of the living brain with positron emission tomography (PET). With this technique, miniscule doses of a radioactively labeled drug are administered to a subject. The drug travels to the brain and binds to specific target sites, called receptors. The distribution and density of these targets in the brain can be measured with a PET camera. An example of this type of work is the measurement of the "dopamine transporter," which is the target site for the action of cocaine. The dopamine transporter is located on dopamine-containing neurons in the brain, and the degeneration of these specific neurons causes the symptoms of Parkinson's disease. Thus, a loss of these target sites can be used to aid in the diagnosis of Parkinson's disease. Although some of the PET radiolabeled drugs might be used for diagnostic purposes, the major use of these agents is to study the pathophysiology of disease. For example, we have implemented a PET probe for the serotonin transporter, which is the target site of antidepressant agents like Prozac. It is unlikely that the levels of the serotonin transporter would aid in diagnosis, but it may well be useful to assess its role in treatment or disease progression. Examples of our findings include: 1) We have found widespread loss of nicotine receptors in the brains of patients with Parkinson's disease. 2) We've studied a promising probe to measure inflammation. 3) We studied a cAMP enzyme involved in intracellular signaling. 4) Contrary to prior studies, we found that patients with alcoholism do not have a deficiency of serotonin transporters.